3,4 Methylenedioxymethamphetamine or MDMA is an illegal hallucinogenic drug that is abused by an ever-increasing number of people. Although MDMA has recently been assigned to the Drug Enforcement Administration classification of Schedule 1, there is a paucity of scientific information regarding its mechanisms of action, neuronal toxicity and addiction liability (i.e., tolerance potential). The specific aims of this proposal include investigations as to the discriminative properties of MDMA in order to determine its mechanism of action, time-course of effect and tolerance production. In addition, the effects of MDMA upon brain neurotransmitters will be determined concurrently with its behavioral actions by the integration of the techniques of in vivo voltammetry and drug discrimination. Pretreatment with known antagonists of either dopaminergic or serotonergic neuronal systems will generate evidence as to exactly how MDMA is acting. Drugs with chemical structures like MDMA have been reported to have actions both upon dopamine (amphetamine-like effects) and serotonin (mescaline-like effects) neurons. Antagonism of these behavioral and neurochemical actions will be attempted by employing available drugs in order to find a therapeutic regimen to counteract possible toxicity. In addition to the behavioral paradigm of drug discrimination other behavioral techniques will be employed to evaluate MDMA's actions. Rotational behavior will be used to evidence its actions upon dopaminergic neurons, whereas self-administration techniques will be used to indicate its abuse potential. Thus, the long-term objectives of this research include gaining a fuller understanding of the central effects of MDMA so as to better characterize and treat its actions in the human abuser.